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Wei-Jie Cheng,1,* Shyr-Yi Lin,2,3,* Kuo-Hsiang Chuang,4,5,* Michael Chen,4 Hsiu-O Ho,1 Ling-Chun Chen,6 Chien-Ming Hsieh,1 Ming-Thau Sheu1 1School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; 2Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan; 5PhD Program in Clinical Drug Development of Chinese Herbal Medicine, Taipei Medical University, Taipei, Taiwan; 6Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan*These authors contributed equally to this workCorrespondence: Chien-Ming Hsieh; Ming-Thau Sheu, Email cmhsieh@tmu.edu.tw; mingsheu@tmu.edu.twIntroduction: Approximately 15%~30% of breast cancers have gene amplification or overexpression of the human epidermal growth factor receptor 2 (HER2), resulting in the chemotherapy resistance, a more-aggressive phenotype and poor prognosis.Methods: We propose a strategy of nanocarriers co-loaded with docetaxel (DTX) and pictilisib (PIC) at a synergistic ratio and non-covalently bound with dual anti-HER2 epitopes bispecific antibodies (BsAbs: anti-HER2-IV/methoxy-polyethylene glycol (mPEG) and anti-HER2-II/methoxy-PEG) for synergistic targeting to overcome the therapeutic dilemmas of the resistance for HER2-targetable chemodrugs. DTX/PIC-loaded nanocarriers (D/P_NCs) were prepared with single emulsion methods and characterized using dynamic light scattering analysis, and the drug content was assayed by high-performance liquid chromatographic method. The integrity and function of BsABs were evaluated using sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked immunosorbent assay (ELISA). The in vitro cell studies and in vivo breast tumor-bearing mice model were used to evaluate the anti-cancer effect and biosafety of formulations.Results: D/P_NCs optimally prepared exhibited a spherical morphology with small particle sizes (~140 nm), high drug loading (~5.5%), and good colloidal stability. The synergistic tumor cytotoxicity of loading DTX and PIC at 2:1 ratio in D/P_NCs was discovered. The BsAbs are successfully decorated on mPEGylated DTX/PIC-loaded nanocarriers via anti-mPEG moiety. In vitro studies revealed that non-covalent decoration with dual BsAbs on D_P-NCs significantly and synergistically increased cellular uptake, while with loading DTX and PIC at a synergistic ratio of 2:1 in D/P_NCs further resulted in synergistic cytotoxicity. In vivo tumor inhibition studies showed the comparable results for synergistic antitumor efficacy while minimizing systemic toxicity of chemodrugs.Conclusion: Non-covalent modification with dual distinct epitopes BsAbs on the nanocarriers loaded with dual chemodrugs at a synergistic ratio was expected to be a promising therapeutic platform to overcome the chemoresistance of various cancers and warrants further development for future therapy in the clinical.Graphical Abstract: Keywords: docetaxel, pictilisib, nanocarriers, bispecific antibodies, dual epitopes, HER2-positive breast cancer

Wei-Jie Cheng,1,* Shyr-Yi Lin,2,3,* Michael Chen,4 Ling-Chun Chen,5 Hsiu-O Ho,1 Kuo-Hsiang Chuang,4,6 Ming-Thau Sheu1 1School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; 2Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4PhD Program in Clinical Drug Development of Chinese Herbal Medicine, Taipei Medical University, Taipei, Taiwan; 5Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 6Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Kuo-Hsiang Chuang; Ming-Thau Sheu Email khchuang@tmu.edu.tw; mingsheu@tmu.edu.twPurpose: This study was aimed at developing the trispecific antibodies (anti-EGFR/anti-FAP/anti-mPEG, TsAb) or dual bispecific antibodies (anti-EGFR/anti-mPEG and anti-FAP/anti-mPEG) docetaxel (DTX)-loaded mPEGylated lecithin-stabilized micelles (mPEG-lsbPMs) for improving the targeting efficiency and therapeutic efficacy.Methods: mPEG-lsbPMs were simply prepared via thin film method. The trispecific antibodies or bispecific antibodies bound the mPEG-lsbPMs by anti-mPEG Fab fragment. The formulations were characterized by DLS and TEM; in vitro and in vivo studies were also conducted to evaluate the cellular uptake, cell cytotoxicity and therapeutic efficacy.Results: The particle sizes of mPEG-lsbPMs with or without the antibodies were around 100 nm; the formulations showed high encapsulation efficiencies of 97.12%. The TsAb and dual bispecific antibodies were fabricated and demonstrated their targeting ability. Two EGFR-overexpressed cell lines (HT-29 and MIA PaCa-2) were co-cultured with FAP-overexpressed WS1 cells (HT-29/WS1; MIA PaCa-2/WS1) to mimic a tumor coexisting in the tumor microenvironment. Cellular binding study revealed that the binding of anti-FAP micelles to three co-culture ratios (4:1, 1:1, and 1:4) of HT-29/EGFR to WS1/FAP was significantly higher than that for TsAb micelles and dual (1:1) micelles, and the binding of those targeting antibodies to WS1/FAP and MIA PaCa-2/EGFR was equally efficacious resulting in a similar binding amount of the TsAb and dual BsAbs (1:1) with the co-culture of MIA PaCa-2/EGFR and WS1/FAP at a 1:1 ratio. Antitumor efficacy study showed that treatment with DTX-loaded mPEG-lsbPMs modified with or without BsAbs, dual BsAbs (1:1), and TsAbs was enhanced in inhibiting tumor growth compared with that for Tynen® while showing fewer signs of adverse effects.Conclusion: Active targeting of both tumors and TAF-specific antigens was able to increase the affinity of DTX-loaded mPEG-lsbPMs toward tumor cells and TAFs leading to successive uptake by tumor cells or TAFs which enhanced their chemotherapeutic efficacy against antigen-positive cancer cells.Keywords: lecithin-stabilized mPEGylated mixed polymeric micelle, bispecific antibody, trispecific antibody, active targeting, tumor-associated fibroblast, tumor antigen

Wei-Jie Cheng,1,* Ling-Chun Chen,2,* Hsiu-O Ho,1 Hong-Liang Lin,3 Ming-Thau Sheu1 1School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; 2Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 3School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan *These authors contributed equally to this work Purpose: In this study, a double emulsion method for complexing plasmids with stearyl polyethylenimine (stPEI) as the core to form human serum albumin (HSA) (plasmid/stPEI/HSA) nanoparticles (NPs) was developed for gene delivery by non-covalently binding onto plasmid/stPEI/HSA nanoparticles with CRISPR/Cas9 or siRNA, which disrupts or silences the expression of programmed cell death ligand-1 (PD-L1) for immunotherapy. Materials and methods: Chemically synthesized stearyl-polyethyenimine (stPEI)/ plasmids /HSA nanoparticles were maded by double emulsion method. They were characterized by dynamic light scattering (DLS), transmission electron microscope and also evaluated by in vitro study on CT 26 cells. Results: stPEI was synthesized by an N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC)–N-hydroxysuccinimide (NHS) reaction, and we found that the degree of substitution was ~1.0 when the ratio of PEI to stearic acid was 1:7 in the reaction. Then, two sgRNA sequences were selected and evaluated for their ability to knock out PD-L1 by decreasing its expression by about 20%. Based on the trend of particle size/zeta potential values as a function of ratio, F25P1 containing 25 µg of plasmid/stPEI/HSA NPs noncovalently bound to 1 µg plasmids via charge–charge interactions was found to be optimal. Its particle size was about 202.7±4.5 nm, and zeta potential was 12.60±0.15 mV. In an in vitro study, these NPs showed little cytotoxicity but high cellular uptake. Moreover, they revealed the potential for transfection and PD-L1 knockout in an in vitro cell model. Furthermore, F25P1S0.5 containing 25 µg of plasmid/stPEI/HSA NPs noncovalently bound to 1 µg of plasmids and 0.5 µg siRNA was prepared to simultaneously deliver plasmids and siRNA. An in vitro study demonstrated that the siRNA did not interfere with the transfection of plasmids and showed a high-transfection efficiency with a synergistic effect on inhibition of PD-L1 expression by 21.95%. Conclusion: The plasmids/stPEI/HSA NPs could be a promising tool for gene delivery and improved immunotherapy. Keywords: stearyl polyethylenimine, human serum albumin nanoparticles, PD-L1, CRISPR, Cas9, siRNA, gene delivery

Changsheng Yan,1 Yi Jiang,1 Yicong Wan,1 Lin Zhang,2 Jinhui Liu,1 Shulin Zhou,1 Wenjun Cheng1 1Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, 2Department of Obstetrics and Gynecology, Zhongda Hospital Affiliated to Southeast University, Medical School, Southeast University, Nanjing, Jiangsu, People’s Republic of China Abstract: Long noncoding RNA (lncRNA) has been proven to be involved in many biological processes in ovarian cancer (OC). However, the mechanism still remains unknown. In this study, we screened significantly downregulated NBAT-1, which has been proven to play a significant role in breast cancer, clear cell renal cell carcinoma, and neuroblastoma, but not in OC, in two independent datasets with relatively more samples (GSE18520 and GSE38666) from Gene Expression Omnibus. We found that lncRNA NBAT-1 was obviously downregulated in OC tissue compared to normal ovarian tissue (P

Neutrophils have a critical role in inflammation. Recent studies have identified their distinctive presence in certain types of atopic dermatitis (AD), yet their exact function remains unclear. This review aims to compile studies elucidating the role of neutrophils in AD pathophysiology. Proteins released by neutrophils, including myeloperoxidase, elastase, and lipocalin, contribute to pruritus progression in AD. Neutrophilic oxidative stress and the formation of neutrophil extracellular traps may further worsen AD. Elevated neutrophil elastase and high-mobility group box 1 protein expression in AD patients' skin exacerbates epidermal barrier defects. Neutrophil-mast cell interactions in allergic inflammation steer the immunological response toward Th2 imbalance and activate the Th17 pathway, particularly in response to allergens or infections linked to AD. Notably, drugs alleviating pruritic symptoms in AD inhibit neutrophilic inflammation. In conclusion, these findings underscore that neutrophils may be therapeutic targets for AD symptoms, emphasizing their inclusion in AD treatment strategies., (© 2024. The Author(s).)

Aim: To investigate the association of long-term care nursing assistants' dual caregiving roles with mental health and to determine whether social support moderates this relationship., Design: A cross-sectional survey., Methods: We surveyed 962 certified long-term care nursing assistants working in long-term care and medical facilities across Taiwan from October 2022 to July 2023. 'Dual caregiving roles' denote the fulfilment of caregiving duties both at work and within families. Mental health was evaluated using the 5-item Brief Symptom Rating Scale. Logistic regression analysis was utilized to investigate the association of dual caregiving roles and psychological job demands with poor mental health. Moreover, we explored whether family, colleague, and supervisor support moderated the association between dual caregiving roles and poor mental health., Results: Among long-term care nursing assistants, 15% had dual caregiving responsibilities. Individuals with both dual caregiving roles and high psychological job demands faced the highest risk of poor mental health compared to those without dual caregiving roles and low psychological job demands. Having dual caregiving roles was associated with poor mental health compared to workers without such roles. Additionally, support from family, colleagues, and supervisors mitigates the association between caregivers' dual caregiving roles and poor mental health., Conclusion: A substantial proportion of long-term care nursing assistants had dual caregiving roles, leading to an additional mental health burden when combined with high psychological job demands. High social support attenuated this association., Implications for the Profession: Long-term care nursing assistants with dual caregiving roles had poorer mental health outcomes. Yet, support from family, colleagues, and supervisors mitigated these effects. These results emphasize the importance of enhancing social support to protect the mental well-being of long-term care nursing assistants managing both formal and informal caregiving duties., Reporting Method: This study adheres to the STROBE guideline of reporting., Patient or Public Contribution: No Patient or Public Contribution., (© 2024 John Wiley & Sons Ltd.)

Background: Toxoplasma gondii, a globally distributed zoonotic obligate intracellular parasite, infects a wide array of mammals, including humans, sheep, and birds. As a unique sheep breed in southwestern China, Yunnan semi-fine wool sheep occupies an important position in animal husbandry in Zhaotong due to its strong adaptability, high reproductive rate, and excellent wool quality. Lambs infected with T. gondii are prone to neurological symptoms and growth retardation, while T. gondii infection in ewes can cause abortions, stillbirths, and deformities, thus affecting sheep reproduction and sheep product quality. Meanwhile, mutton and dairy products contaminated with T. gondii can become potential sources of human infection, potentially threatening public health and safety., Method: To understand the T. gondii infection in semi-fine wool sheep in Zhaotong, Yunnan Province, 586 blood samples were collected and subjected to indirect hemagglutination assay (IHA) for T. gondii antibodies, and the infection-related factors were analyzed through cross-sectional analysis. In the meantime, nested PCR was conducted on a total of 217 samples collected from 31 rodents caught in and around the sheep breeding ground to test the T. gondii B1 gene in rodent tissues., Results: A total of 94 sera tested positive for T. gondii antibodies, with a total positive rate of 16.04% (94/586) (95% CI: 14.77-20.89). Cross-sectional statistical analysis on factors related to semi-fine wool sheep infection rate, including sampling season, sex, age, and weight, suggested that age (< 6 months: 23.81%; 6-12 months: 11.74%; > 12 months: 15.83%) was a significant factor explaining the infection rate differences (P = 0.003 < 0.05, χ 2  = 11.62, df = 2). Thus, age was considered a key risk factor for T. gondii infection in this study (odds ratio, OR = 2.35, 95% CI: 1.42-3.87). Nested PCR analysis on 217 (heart, liver, spleen, lung, kidney, brain, and muscle) tissues from the 31 rodents indicated that 11 tested positive. The total infection rate of rodents in and around the breeding ground was 35.48% (11/31), and 14 samples tested positive, with a positive infection rate of 6.45% (14/217)., Conclusion: The T. gondii infection rates of semi-fine wool sheep and rodents from their breeding environment in Zhaotong, Yunnan Province, were high, necessitating enhanced prevention, control, and treatment measures to ensure the healthy breeding of semi-fine wool sheep and veterinary public health and safety., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Study Objectives: Obstructive sleep apnea (OSA) is more prevalent in men and older adults. Few studies have explored variations in pathological endotypic traits by age and sex using a large patient sample, offering insights into the development of the disease. Our study aims to examine how endotype characteristics of obstructive sleep apnea vary across age in different sex., Methods: A cross-sectional study was conducted, enrolling 2296 adult patients referred for in-laboratory diagnostic polysomnography at a single sleep center in Taiwan. Among them, 1374 had an apnea-hypopnea index ≥ 5. Using the "Phenotyping Using Polysomnography" method, we estimated four endotypic traits-arousal threshold, upper airway collapsibility, loop gain, and upper airway muscle compensation. Demographic and polysomnographic characteristics were compared between sexes and age groups. Generalized linear regression and generalized additive models were employed to explore the associations of sex and age with endotypic traits., Results: Men with OSA exhibited higher collapsibility and lower compensation than women (difference: 4.32 %eupnea and 4.49 %eupnea, respectively). Younger patients with OSA had a higher prevalence of obesity, more snoring symptoms, and lower loop gain compared to older patients. For men, age was correlated with increased collapsibility, increased loop gain, and decreased arousal threshold after 37 years old. Whereas in women, endotypic traits were not associated with age, except for an increase in loop gain with advancing age., Conclusions: Personalized treatment options for OSA should take into consideration age and sex. Reducing loop gain could be a treatment objective for older patients with OSA., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: The aim of our study is to explore the associations between multiple types of workplace violence (WPV) and burnout risk, sleep problems, and leaving intention among nurses., Methods: This cross-sectional survey recruited 1,742 nurses, and data on WPV experiences were collected through self-administered questionnaires. Work conditions, burnout risk scales, sleep quality, and leaving intentions were also evaluated. Multivariate logistic regression analyses were performed to examine the associations of WPV with burnout risk, sleep quality, and leaving intentions, adjusting for demographic characteristics and work conditions., Results: The study found that 66.7% of nurses reported experience of WPV, with 26.9% experiencing both physical and nonphysical forms. Those who experienced multiple types of WPV reported worse work conditions, higher burnout risk, poorer sleep quality, and a stronger leaving intention compared to those without such experiences. Adjusting for working conditions, logistic regression analysis showed that nurses who experienced multiple types of WPV had 2.12-fold higher odds of high personal burnout risk, 2.36-fold higher odds of high client-related burnout risk, 1.95-fold higher odds of poor sleep quality, and 1.80-fold higher odds of high leaving intention, compared to those without WPV experiences., Conclusions: Strategies by hospital managers and policymakers to monitor and reduce workplace violence are vital for sustaining nurses' mental health, well-being, and preventing early attrition from the profession., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Occupational Hygiene Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Early retirement is highly prevalent in Taiwan. This study assesses the association between early retirement and all-cause and cause-specific mortality risks while exploring the modifying effect of sociodemographic factors., Methods: Using Taiwan's National Health Insurance Research Database between 2009 and 2019, 1 762 621 early retirees aged 45-64 and an equal number of employed comparators were included. The date and cause of death were identified using the National Death Registry. Cox regression models were used to estimate HRs of early retirement for all-cause mortality and cause-specific mortality. To explore modifying effects, we conducted subgroup analyses based on age groups, sexes, occupation types and general health status (Charlson Comorbid Index score)., Results: The analysis revealed that early retirees, compared with their concurrently employed counterparts, had a higher mortality risk (adjusted HR (aHR) 1.69, 95% CI (1.67 to 1.71)). Specifically, younger individuals (aged 45-54) (aHR 2.74 (95% CI 2.68 to 2.80)), males (aHR 1.78 (95% CI 1.76 to 1.81)), those in farming or fishing occupations (aHR 2.13 (95% CI 2.06 to 2.21)) or the private sector (aHR 1.92 (95% CI 1.89 to 1.96)), and those with the poorest health conditions (aHR 1.79 (95% CI 1.76 to 1.83)) had higher mortality risks of early retirement. Regarding specific causes of death, the top three highest risks were associated with gastrointestinal disorders, followed by suicide and neurological disorders., Conclusions: This study underscores the substantial mortality risk increase linked to early retirement, emphasising the importance of policy considerations, particularly regarding vulnerable populations and specific causes of death potentially linked to unhealthy lifestyles., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the effect of selenium on cyclophosphamide (CTX)-induced spermatogenic impairment (SI) in mice and its underlying mechanism., Methods: We equally randomized 36 male KM mice into 3 SI model and 3 control groups, the first 3 treated by intraperitoneal injection of CTX at 100 mg/kg (the SI model control group), CTX plus SI model control group, selenium deficient model group (－Se SI), selenium supplemented model group (+Se SI), while latter 3 by intraperitoneal injection of normal saline (the normal control), selenium deficiency control group (－Se control), selenium addition control group (+Se control), respectively, all once a week for 6 successive weeks. Then we observed the histopathological changes in the testes of all the mice by HE staining, obtained the sperm count in the epididymides, determined the expressions of glutathione peroxidase 4 (GPx4) and SLC7A11 proteins by Western blot and ferroptosis-related genes by RT-qPCR, and examined the changes in the expressions of ferroptosis-related proteins and genes in the GC2-spd cells treated with ferroptosis inhibitors and inducers in combination with different concentrations of inorganic sodium selenite (SeS) and organic selenomethionine (SeM)., Results: Compared with the normal controls, the SI model mice showed significantly decreased testicular and prostatic organ coefficients, reduced spermatogenic layers, increased voids, decreased serum ferritin concentration (P<0.05), and elevated transferrin concentration (P<0.05). The organ coefficients were significantly higher in the +Se SI and +Se control than in the －Se SI and －Se control groups (P<0.05, P<0.01), with evident pathological improvement of the testis tissue in the +Se controls. The expressions of the GPx4 and solute carrier family 7 members 11（SLC7A11） genes in the testis were dramatically down-regulated in the SI model controls (P<0.01), but up-regulated in the +Se SI and +Se control compared with those in the －Se SI and －Se control group (P<0.01 and P<0.05), but there were no statistically significant differences between their protein expressions. The results of in vitro GC2 spd cell experiments indicated that the GPx4 gene and GPx4 protein levels in the - Se group were significantly lower than those in the normal control group (P<0.05), while the SLC7A11 gene level decreased (P<0.01). Different doses of SeS and SeM significantly increased the GPx4 protein expression compared to the average Se group. Low doses of SeM promoted a significant increase in GPx4 gene levels, while high doses of SeS increased the expression levels of SLC7A11 gene and SLC7A11 protein (P<0.05, P<0.01). The Se group showed a significant decrease in the levels of acsl4 and ptgs2 genes compared to the normal control group. SeM promoted the expression of acsl4, while SeS promoted the expression of ptgs2 and fth1 (P<0.01, P<0.05). The intervention results of GC2 spd showed that the Erastin group had a decrease in ptgs2 compared to the normal control group, while the SeS+Erastin and SeM+Erastin groups had an increase in ptgs2 gene expression compared to the Erastin group. However, the ptgs2 expression of Fer-1 was lower than that of the normal control group, and the ptgs2 gene level of SeS+Fer-1 and SeM+Fer-1 groups was lower than that of Fer-1 group (P<0.05); The gene quantity of GPx4 in the SeM+Erastin and SeM+Fer-1 groups increased compared to the Erastin and Fer-1 groups (P<0.01, P<0.05); SeM+Erastin and SeS+Erastin showed a decrease in SLC7A11 compared to the Erastin group, as well as SeM+Fer-1 and SeS+Fer-1 groups compared to the Fer-1 group, accompanied by an increase in acsl4 and fth1 (P<0.01)., Conclusion: Selenium deficiency causes the reduction of the SLC7A11 and GPx4 gene levels, disorder of ferroptosis-related genes and down-regulation of the GPx4 protein expression in the mouse testis and spermatocytes. Selenium can promote the expression of GPx4, up-regulate the level of SLC7A11, and improve spermatogenesis in the testis of the mouse with SI. There are differences between organic SeM and inorganic SeS in regulating the ferroptosis pathway-related genes.

Background: There is a lack of information regarding outcomes of elderly patients hospitalized with COVID-19 following the widespread use of COVID-19 vaccines and antiviral agents., Methods: A retrospective study was conducted between January and August 2022, enrolling patients aged 65 years or older. Patients were categorized into two groups: 'old' (65-79 years) and 'oldest-old' (80 years or more). Multivariate regression was employed to identify independent prognostic factors for in-hospital mortality., Results: A total of 797 patients were enrolled, including 428 old and 369 oldest-old patients. In each subgroup, 66.6 % and 59.6 % of patients received at least one dose of the COVID-19 vaccine, respectively. Approximately 40 % of the patients received oral antiviral agents either before or upon hospital admission. A greater percentage of the oldest-old patients received remdesivir (53.4 % versus 39.7 %, p < 0.001), dexamethasone (49.3 % versus 36.7 %, p < 0.001), and tocilizumab (10.0 % versus 6.8 %, p < 0.001) than old patients. The mortality rate was comparable between the two age subgroups (14 % versus 15.2 %). Independent predictors of in-hospital mortality included disease severity and comorbidities such as end-stage renal disease (ESRD), cirrhosis, solid tumours, and haematologic malignancies. Ageing was not correlated with increased in-hospital mortality across all comorbidity subgroups., Conclusions: In the later stages of the pandemic, with widespread vaccination and advancements in COVID-19 treatments, outcomes for hospitalized elderly and oldest-old patients with COVID-19 have improved. The influence of age on in-hospital mortality has diminished, while comorbidities such as ESRD, cirrhosis, solid tumours, and hematologic malignancies have been associated with mortality., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Over half of all cases of obstructive sleep apnoea (OSA) are classified as supine-related OSA; however, the pathological endotype during supine position is not fully understood. This study aims to investigate the endotypic traits of supine-predominant OSA and explore the variations in endotypic traits between the supine and lateral positions., Methods: We prospectively recruited 689 adult patients with OSA from a single sleep centre between April 2020 and December 2022. Endotypic traits, namely arousal threshold, collapsibility, loop gain and upper airway muscle compensation, were retrieved from polysomnographic signals. We identified spOSA by a supine to non-supine apnoea-hypopnoea index (AHI) ratio >2. We cross-sectionally compared demographic and endotypic traits between supine-predominant OSA and non-positional OSA and examined the associations between supine-predominant OSA and endotypic traits. Additionally, we compared the changes in endotypic traits between supine and lateral positions in patients with supine-predominant OSA and non-positional OSA., Results: In our study sample, 75.8% of patients were identified as having supine-predominant OSA. Compared to non-positional OSA, supine-predominant OSA was associated with low collapsibility (β= -3.46 % eupnoea , 95% CI -5.93- -1.00 % eupnoea ) and reduced compensation (β= -6.79 % eupnoea , 95% CI -10.60- -2.99 % eupnoea ). When transitioning from the lateral to supine position, patients with supine-predominant OSA had a substantial decrease in compensation compared to those with non-positional OSA (-11.98 versus -6.28 % eupnoea )., Conclusions: Supine-predominant OSA is the prevalent phenotype of OSA in Asian patients. Inadequate upper airway compensation appears to be a crucial underlying pathology in patients with supine-predominant OSA., Competing Interests: Conflict of interest: S.A. Sands received grant support from Apnimed, Prosomnus and Dynaflex, and has served as a consultant for Apnimed, Nox Medical, Inspire Medical Systems, Merck, Eli Lilly, Respicardia, LinguaFlex and Forepont; his interactions with industry are managed by his institution. E. Finnsson and J.S. Ágústsson are employees of Nox Medical. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Determining the endotypes of obstructive sleep apnea (OSA) has potential implications for precision interventions. Here we assessed whether continuous positive airway pressure (CPAP) treatment outcomes differ across endotypic subgroups. We conducted a retrospective analysis of data obtained from 225 patients with moderate-to-severe OSA from a single sleep centre. Polysomnographic and CPAP titration study data were collected between May 2020 and January 2022. One-month CPAP treatment adherence was followed. Obstructive sleep apnea endotypes, namely arousal threshold, collapsibility, loop gain, and upper airway gain were estimated from polysomnography and dichotomised as high versus low. We examined associations between endotypic subgroups and (1) optimal CPAP titration pressure, (2) CPAP-related improvements in sleep architecture (proportions of slow-wave and rapid eye movement (REM) sleep), and (3) CPAP adherence. We observed that patients with high collapsibility required a higher CPAP pressure than those with low collapsibility (∆ = 0.4 cmH 2 O, 95% confidence interval [CI] = 0.3-1.7). A larger increase in slow-wave sleep and in REM sleep proportions after CPAP treatment were observed in patients with a high arousal threshold, high collapsibility, high loop gain, or high upper airway gain than in those with low levels of endotypes. High loop gain and high collapsibility were independently associated with longer CPAP use hours per night (∆ = 0.6 h, 95% CI = 0.2-1.5 and ∆ = 0.3 h, 95% CI = 0.03-1.5, respectively). In conclusion, different endotypic subgroups of OSA exhibit a difference in outcomes of CPAP treatment. Knowledge of endotypes may help clinicians to understand which patients are expected to benefit most from CPAP therapy prior to its administration., (© 2023 European Sleep Research Society.)

Objective: To investigate the occurrence of depressive disorders spanning the transition to retirement, and explore the relationship between retirement age and depressive disorders., Methods: We utilized a national population-based health insurance database encompassing 2 million Taiwanese individuals from 2000 to 2019. The study focused on individuals aged 50 years and older who were employed at the baseline, and 84,224 individuals had records of retirement during the follow-up period. Depressive disorders were identified using codes from the International Classification of Diseases. To assess the trend in the incidence of depressive disorders 7-year period before and after retirement, an interrupted time series analysis was performed. Cox-proportional hazard models were employed to investigate the association between retirement age and the occurrence of depressive disorders following retirement., Results: The incidence of depression peaks at the time of retirement and shows a significant decrease after retirement. Incidence of depressive disorders was 6.4 and 7.6 per 1000 person-years among individuals who retired between the ages of 60-64 and 65-69. Comparing the two groups, those who retired between 65 and 69 exhibits a higher risk of developing depressive disorders (hazard ratio = 1.10, 95% confidence interval = 1.02-1.18). This association is particularly pronounced among women and individuals residing in areas with low urbanization levels., Conclusion: Retirement marks a crucial life milestone accompanied by a peak in depressive disorders. It is important to address the higher risk of depression associated with late retirement among socially disadvantaged groups., Competing Interests: DISCLOSURES This work was supported byChina Medical University Hospital[grant numberDMR-111-105;DMR-112-087] andNational Health Research Institutes[grant number12A1-CGGP06-051]. The funders have no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. We are grateful toHealth Data Science Center, China Medical University Hospitalfor providing administrative, technical and funding support. All authors declare no conflicts of interest related to this study., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Dietary patterns and corresponding gut microbiota profiles are associated with various health conditions. A diet rich in polyphenols, primarily plant-based, has been shown to promote the growth of probiotic bacteria in the gastrointestinal tract, subsequently reducing the risk of metabolic disorders in the host. The beneficial effects of these bacteria are largely due to the specific metabolites they produce, such as short-chain fatty acids and membrane proteins. In this study, we employed a metabolomics-guided bioactive metabolite identification platform that included bioactivity testing using in vitro and in vivo assays to discover a bioactive metabolite produced from probiotic bacteria. Through this approach, we identified 5'-methylthioadenosine (MTA) as a probiotic bacterial-derived metabolite with anti-obesity properties. Furthermore, our findings indicate that MTA administration has several regulatory impacts on liver functions, including modulating fatty acid synthesis and glucose metabolism. The present study elucidates the intricate interplay between dietary habits, gut microbiota, and their resultant metabolites.

Background: As the largest substantive organ of animals, the liver plays an essential role in the physiological processes of digestive metabolism and immune defense. However, the cellular composition of the pig liver remains poorly understood. This investigation used single-nucleus RNA sequencing technology to identify cell types from liver tissues of pigs, providing a theoretical basis for further investigating liver cell types in pigs., Results: The analysis revealed 13 cells clusters which were further identified 7 cell types including endothelial cells, T cells, hepatocytes, Kupffer cells, stellate cells, B cells, and cholangiocytes. The dominant cell types were endothelial cells, T cells and hepatocytes in the liver tissue of Dahe pigs and Dahe black pigs, which accounts for about 85.76% and 82.74%, respectively. The number of endothelial cells was higher in the liver tissue of Dahe pigs compared to Dahe black pigs, while the opposite tendency was observed for T cells. Moreover, functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic endothelial cells were significantly enriched in the protein processing in endoplasmic reticulum, MAPK signaling pathway, and FoxO signaling pathway. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic T cells were significantly enriched in the thyroid hormone signaling pathway, B cell receptor signaling pathway, and focal adhesion. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic hepatocytes were significantly enriched in the metabolic pathways., Conclusions: In summary, this study provides a comprehensive cell atlas of porcine hepatic tissue. The number, gene expression level and functional characteristics of each cell type in pig liver tissue varied between breeds., (© 2023. The Author(s).)

Background: As the world's population of people vaccinated with the COVID-19 vaccine increases, adverse reactions are increasingly being reported. There have been progressive reports of the effects of COVID-19 vaccination on cosmetic fillers or prostheses, but they have not been reviewed based on their clinical morphologic patterns. This article reviewed the progress of research on adverse reactions to cosmetic implants after COVID-19 vaccination., Methods: We researched the English-language literature up to October 15, 2022, using predefined keywords to identify relevant studies about adverse reactions to cosmetic implants after the COVID-19 vaccination, collecting patient characteristics, implant type, the time interval between vaccination and implantation or injection, time of onset, symptoms, treatments, and outcomes., Results: Among the adverse reactions to implants associated with COVID-19 vaccination, we distinguished between (1) injectable fillers and (2) surgical prosthetic implants. The most common adverse reactions were at the site of hyaluronic acid injection and breast prosthesis after Pfizer vaccination, mainly DIRs, and mainly manifested as edema, rash, fever, and capsular contracture. This paper also reported the possible causes, treatments of DIRs, and limitations of current studies., Conclusions: In this article, we attempted to investigate and discuss all the adverse reactions of cosmetic implants related to COVID-19 vaccination in the current literature, to unmask these reactions and make a more accurate assessment of vaccine safety., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

The purpose of this study was to develop poloxamer (P407)-based in-situ thermogellable hydrogels with reducing concentration of P407 by adding hypromellose (HPMC) and with enhancing mucoadhesion of resulting hydrogels by adding hyaluronic acid (HA) for prolonging ocular delivery of hydroxypropyl-β-cyclodextrin (HPβCD)-solubilized testosterone (TES). Results demonstrated that 0.5% TES solution was successfully solubilized with adding 10% HPβCD. Non-gellable 13% P407 sol became in-situ gellable with adding 2.0-2.5% HPMC and mucoadhesibility was further imporved with adding 0.3% HA-L (low MW) or HA-H (high MW). Optimized 0.5% HPβCD-solubilized TES P407-based thermogellable hydrogels with enhancement of mucoadhesion for prolonging ocular delivery comprised 13% P407, 2.5% HPMC, and 0.3% HA-L or HA-H. Furthermore, rheological measurements under simulated eye blinking confirmed that non-thixotropic properties of optimized hydrogels could be spreaded evenly and retain a greater amount of drug-loaded hydrogels on the ocular surface for a longer period to prolong drug delivery. Compared with conventional eye drops, the prolonged residence time of optimized hydrogels from ex vivo and in vivo studies were observed, indicating relationships between rheological properties and in vivo performances. It was concluded that P407-based thermosensitive hydrogels with reducing concentration of P407 and enhancing mucoadhesion was successfully formulated by adding 2.5% HPMC and 0.3% HA in 13% P407 for potentially accomplishing effective clinical treatment of DED.

Background: Coronavirus disease 2019 (COVID-19) has been found to have a greater impact on individuals with pre-existing psychiatric disorders. However, the underlying reasons for this increased risk have yet to be determined. This study aims to investigate the potential factors contributing poor outcomes among COVID-19 patients with psychiatric disorders, including delayed diagnosis of infection, vaccination rates, immune response, and the use of psychotropic medications., Methods: This retrospective cohort study analyzed medical records of 15,783 adult patients who were diagnosed with COVID-19 infection by positive PCR tests between January and September 2022 at a single medical center. We identified psychiatric diagnoses using ICD-9 diagnostic codes from the preceding 3 years before COVID infection. Primary outcome was in-hospital mortality and secondary outcomes were severe illness requiring intensive care or mechanical ventilation, and hospitalization within 45 days after a positive COVID-19 test. We compared the rates of outcomes, viral load, vaccination status at the time of positive test, psychotropic medications prescription within 90 days prior, antiviral medication use, and blood inflammation markers between patients with and without psychiatric disorders. The Cox proportional hazard model was used to examine the association of psychiatric diagnoses, vaccination status, and psychotropic medication prescription with poor outcomes., Results: Patients with psychiatric disorders demonstrated higher rates of severe illness (10.4% v.s. 7.1%) and hospitalization (16.4% vs. 11.3%), as well as a shorter duration to in-hospital mortality (6 vs. 12.5 days) compared to non-psychiatric patients. Psychiatric patients had higher vaccination rates and lower levels of inflammatory markers than non-psychiatric patients. Antipsychotic medication use was associated with in-hospital mortality (hazard ratio [HR] = 4.79, 95% confidence interval [CI] = 1.23-18.7), while being unvaccinated was associated with hospitalization (HR = 1.81, 95% CI = 1.29 to 2.54) and severe illness (HR = 3.23, 95% CI = 1.95 to 5.34) among patients with psychiatric disorders. Sedatives prescription was associated with all poor outcomes in general patients., Conclusion: Considering the narrow time window between a positive COVID-19 test and poor outcomes, healthcare providers should undertake close monitoring of patients with preexisting psychiatric disorders during the initial days after a positive PCR test. Furthermore, caution should be taken when prescribing psychotropic medications, with special attention to antipsychotics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: One aspect of work sustainability pertains to workers' intention to remain in their current job until reaching retirement age. Various adverse working conditions are expected to diminish work sustainability among different social groups. This study aims to examine these associations across gender and age groups., Methods: The study participants were 19,152 economically-active adults in a national survey conducted in Taiwan. Information concerning psychosocial working conditions were obtained through interviews, using the Job Content Questionnaire. Work sustainability was evaluated by one question that asked whether the participants felt they would be able to do their current job until the age of 60. The association between psychosocial work conditions and work sustainability was examined by logistic regression analysis. We further performed stratified analysis to explore age and gender-specific associations., Results: We observed that 14.2% and 17.1% of male and female workers reported low work sustainability. Workers in the electronics industries and female workers in the healthcare and education sectors reported low work sustainability. Gender-specific analyses showed that low job control among men and shift work among women were significantly associated with low work sustainability. Age-specific analyses indicated that having poor health, shift work, and long working hours in younger workers, and having low job control in older workers were associated with low work sustainability., Conclusion: To retain older workers in the labor market, policies should aim at the improvement of psychosocial work conditions, and gender- and age-specific issues should be taken into consideration., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Head and neck cancer (HNC) is a prevalent malignancy with a poor prognosis, necessitating the identification of prognostic biomarkers to guide management. The geriatric nutritional risk index (GNRI), calculated from serum albumin and body weight, may predict survival in patients with HNC. We performed a systematic review and meta-analysis to clarify this relationship. Databases were searched for studies examining the association between pretreatment GNRI and overall survival in patients with HNC. Ten studies with 2793 patients were included. Meta-analysis demonstrated that low GNRI was associated with significantly worse overall survival compared to high GNRI (hazard ratio [HR]:2.84, 95% CI 2.07-3.91, p < 0.00001). Older age (HR:1.73; 95% CI, 1.35-2.22; p < 0.0001), male sex (HR:1.7; 95% CI, 1.12-2.6; p = 0.01), advanced tumor stage (HR: 2.5; 95% CI, 1.72-3.63; p < 0.00001), and higher T-/ N -stage (HR = 1.69 and 1.98, respectively) were also predictive of unfavorable outcomes. The GNRI had the highest HR, suggesting potent predictive ability. Despite limitations, including retrospective design and potential publication bias, our study indicates that low pretreatment GNRI predicts poor overall survival in patients with HNC. The GNRI is an inexpensive, routinely available biomarker that could improve prognostication and guide management decisions. Additional research is warranted to validate these findings.

The aim of this meta-analysis was to assess the association of general anesthesia (GA) exposure with the risk of POD in this patient population. Databases including Medline, EMBASE, Cochrane library, and Google Scholar were searched from inception to December 2022. Analysis of 17 studies published between 2015 and 2021 involving 10,678 individuals revealed an association of GA exposure with an elevated risk of POD [odd ratio (OR) = 1.846, 95% CI 1.329 to 2.563, p = 0.0003, I 2  = 68.4%, 10,678 patients]. Subgroup analysis of the diagnostic methods also demonstrated a positive correlation between GA exposure and POD risk when validated methods were used for POD diagnosis (OR = 2.199, 95% CI 1.46 to 3.31, p = 0.0002). Meta-regression analyses showed no significant impact of age, male proportion, and sample size on the correlation between GA and the risk of POD. The reported overall incidence of POD from the included studies regardless of the type of anesthesia was between 0.8 and 27%. Our meta-analysis showed a pooled incidence of 10.3% (95% CI 7% to 15%). This meta-analysis suggested an association of general anesthesia with an elevated risk of postoperative delirium, implying the necessity of implementing appropriate prophylactic strategies against this complication when general anesthesia was used in this clinical setting., (© 2023. The Author(s).)

Background: Eimeria tenella is an obligate intracellular parasitic protozoan that invades the chicken cecum and causes coccidiosis, which induces acute lesions and weight loss. Elucidating the anticoccidial mechanism of action of green tea polyphenols could aid the development of anticoccidial drugs and resolve the problem of drug resistance in E. tenella., Methods: We constructed a model of E. tenella infection in Wuliangshan black-boned chickens, an indigenous breed of Yunnan Province, China, to study the efficacy of green tea polyphenols against the infection. Alterations in gene expression and in the microbial flora in the cecum were analyzed by ribonucleic acid (RNA) sequencing and 16S ribosomal RNA (rRNA) sequencing. Quantitative real-time polymerase chain reaction was used to verify the host gene expression data obtained by RNA sequencing. Network pharmacology and molecular docking were used to clarify the interactions between the component green tea polyphenols and the targeted proteins; potential anticoccidial herbs were also analyzed., Results: Treatment with the green tea polyphenols led to a reduction in the lesion score and weight loss of the chickens induced by E. tenella infection. The expression of matrix metalloproteinase 7 (MMP7), MMP1, nitric oxide synthase 2 and ephrin type-A receptor 2 was significantly altered in the E. tenella infection plus green tea polyphenol-treated group and in the E. tenella infection group compared with the control group; these genes were also predicted targets of tea polyphenols. Furthermore, the tea polyphenol (-)-epigallocatechin gallate acted on most of the targets, and the molecular docking analysis showed that it has good affinity with interferon induced with helicase C domain 1 protein. 16S ribosomal RNA sequencing showed that the green tea polyphenols had a regulatory effect on changes in the fecal microbiota induced by E. tenella infection. In total, 171 herbs were predicted to act on two or three targets in MMP7, MMP1, nitric oxide synthase 2 and ephrin type-A receptor 2., Conclusions: Green tea polyphenols can directly or indirectly regulate host gene expression and alter the growth of microbiota. The results presented here shed light on the mechanism of action of green tea polyphenols against E. tenella infection in chickens, and have implications for the development of novel anticoccidial products., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Rationale: Obstructive sleep apnea (OSA) is a heterogeneous syndrome with various endotypic traits and symptoms. A link among symptoms, endotypes, and disease prognosis has been proposed but remains unsupported by empirical data. Objectives: To link symptom profiles and endotypes by clustering endotypic traits estimated using polysomnographic signals. Methods: We recruited 509 patients with moderate to severe OSA from a single sleep center. Polysomnographic data were collected between May 2020 and January 2022. Endotypic traits, namely arousal threshold, upper airway collapsibility, loop gain, and upper airway muscle compensation, were retrieved using polysomnographic signals during non-rapid eye movement periods. We used latent class analysis to group participants into endotype clusters. Demographic and polysomnographic parameter differences were compared between clusters, and associations between endotype clusters and symptom profiles were examined using logistic regression analyses. Results: Three endotype clusters were identified, characterized by high collapsibility/loop gain, low arousal threshold, and low compensation, respectively. Patients in each cluster exhibited similar demographic characteristics, but those in the high collapsibility/loop gain cluster had the highest proportion of obesity and severe oxygen desaturation observed in polysomnographic studies. The low compensation cluster was characterized by fewer sleepy symptoms and exhibited a lower rate of diabetes mellitus. Compared with the excessively sleepy group, disturbed sleep symptoms were associated with the low arousal threshold cluster (odds ratio, 1.89; 95% confidence interval, 1.16-3.10). Excessively sleepy symptoms were associated with the high collapsibility/loop gain cluster (odds ratio, 2.16; 95% confidence interval, 1.39-3.37) compared with the minimally symptomatic group. Conclusions: Three pathological endotype clusters were identified among patients with moderate to severe OSA, each exhibiting distinct polysomnographic characteristics and clinical symptom profiles.

In this study, an ultrasound-assisted digestion method of a formic acid-decellularized extracellular matrix (dECM) of porcine skin was developed and optimized to form UdECM hydrogels for diabetic wound healing. Results demonstrated that ultrasonication improved the extraction rate of collagen from dECM samples, preserved the collagen content of dECM, reduced residual cells, and extracted greater DNA contents. Scanning electron microscope (SEM) analyses were performed, which demonstrated the optimal porosity on the surface and density of the cross-section in the hydrogel structure, which could control the release of growth factors embedded in UdECM hydrogels at desirable rates to boost wound healing. A wound-healing study was conducted with six different composite hydrogels, both empty materials and materials enriched with rat platelet-rich plasma (R-PRP), sacchachitin nanofibers (SCNFs), and TEMPO-oxidized sacchachitin in diabetic rats. The assessment based on scars stained with hematoxylin and eosin (H&E), Masson's trichrome (MT), and a cluster of differentiation 31 (CD31) staining showed that the UdECM/SC/R-PRP treatment group had the most significant efficacy of promoting healing and even recovery of diabetic wounds to normal tissues. UdECM/R-PRP and UdECM/SCNFs demonstrated better healing rates than UdECM hydrogel scaffolds, which had only recovered 50% resemblance to normal skin. Treatment with both UdECM/TEMPO 050 and UdECM/TEMPO 050/R-PRP hydrogel scaffolds was ranked last, with even poorer efficacy than UdECM hydrogels. In summary, formulated UdECM and SCNF hydrogels loaded with PRP showed synergistic effects of accelerating wound healing and ultimately stimulating the wound to recover as functional tissues. This newly UdECM/SCNF composite hydrogel has promising potential for healing and regenerating diabetic wounds.

Introduction: Patients with depressive disorder demonstrate rest-activity rhythm disturbances and cognitive function impairment. This study examined the association of individual rest-activity rhythm changes over time with mood symptoms and attention., Methods: We recruited 15 adult outpatients with a diagnosis of major depressive disorder from a single medical center and observed them for 12 months. Weekly rest-activity parameters, including rhythm characteristics generated from nonparametric circadian rhythm analysis, were retrieved from actigraphy data. Attention was evaluated weekly with a smartphone-based psychomotor vigilance test upon awakening. Depressive symptom severity was evaluated using the Beck Depression Inventory (BDI) fortnightly. The association of rest-activity parameters with BDI score and attention was examined using generalized linear mixed regression. A fixed-effects analysis was used to examine the association between rest-activity parameters and depressive episodes., Results: An advanced bedtime and most active continuous 10 h starting time were associated with depressive symptom severity but also associated with higher vigilance test performance. A longer sleep duration, mainly due to an earlier bedtime, was associated with depressive symptom severity. Compared to remission, sleep duration was 27.8 min longer during depressive episodes, and bed time was 24 min earlier. A shorter sleep duration and increased activity during sleep were associated with poorer attention., Discussion: Rest-activity rhythms change with mood symptoms among patients with depressive disorder. The circadian rhythms of rest-activity among patients with depressive disorder should be distinguished during various mood states in future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Cheng, Hsiao, Huang, Kubo, Hang and Lee.)

This meta-analysis aimed to assess the clinical association of the preoperative prognostic nutritional index (pre-PNI) with the risk of postoperative acute kidney injury. Four databases (e.g., Medline) were searched from inception to December 2022 to investigate the association between pre-PNI (i.e., low vs. high) and PO-PNI as well as the correlation between pre-PNI and other postoperative prognostic indices. Overall, 13 observational studies, including 9185 patients, were eligible for analysis. A low PNI was related to increased risks of PO-AKI [odd ratio (OR) = 1.65, p = 0.001, 3811 patients], postoperative infection (OR = 2.1, p < 0.00001, 2291 patients), and mortality (OR = 1.93, p < 0.0001, 2159 patients). Albeit statistically nonsignificant, a trend was noted, linking a low PNI to higher risks of postoperative bleeding (OR = 2.5, p = 0.12, 1157 patients) and stroke (OR = 1.62, p = 0.07, 2036 patients). Pooled results revealed a prolonged intensive care unit (ICU) stay in patients with low PNIs compared to those with high PNIs (MD: 0.98 days, p = 0.02, 2209 patients) without a difference in hospital stay between the two groups (MD: 1.58 days, p = 0.35, 2249 patients). This meta-analysis demonstrated an inverse correlation between PNI and the risks of PO-AKI, postoperative infection, and mortality, as well as the length of ICU stay, which warrants further investigations for verification.

Background: Stroke may cause debilitating neurological deficiencies that result in motor, sensory, and cognitive deficits and poorer psychosocial functioning. Prior studies have provided some initial evidence for the significant roles of health literacy and poor oral health for old people. However, few studies have focused on the health literacy of individuals who had a stroke; therefore, the relationships between the health literacy and oral health-related quality of life (OHRQoL) among middle-aged and older adults who had a stroke are unknown. We aimed to assess the relationships between stroke prevalence, health literacy status, and OHRQoL in middle-aged and older adults., Methods: We retrieved the data from The Taiwan Longitudinal Study on Aging, a population-based survey. For each eligible subject, we gathered data in 2015 on age, sex, level of education, marital status, health literacy, the activity daily living (ADL), stroke history and OHRQoL. We evaluated the respondents' health literacy by using a nine-item health literacy scale and categorized their health literacy level as low, medium, or high. OHRQoL was identified based on the Taiwan version of the Oral Health Impact Profile (OHIP-7T)., Results: The final study contained 7702 community-based dwelling elderly people (3630 male and 4072 female) were analysis in our study. Stroke history was reported in 4.3% of participants, 25.3% reported low health literacy, and 41.9% had at least one ADL disability. Furthermore, 11.3% of participants had depression, 8.3% had cognitive impairment, and 3.4% had poor OHRQoL. Age, health literacy, ADL disability, stroke history, and depression status were significantly associated with poor OHRQoL after sex and marital status was adjusted. Medium (odds ratio [OR] = 1.784, 95% confidence interval [CI] = 1.177, 2.702) to low health literacy (OR = 2.496, 95% CI = 1.628, 3.828) was significantly associated with poor OHRQoL., Conclusions: Base our study results, people with stroke history had poor OHRQoL. Lower health literacy and ADL disability were associated with worse QHRQoL. Further studies are necessary to define practical strategies for reducing the risk of stroke and oral health with constantly lower health literacy, thereby improving the quality of life and providing health care of older people., (© 2023. The Author(s).)

Objective: To investigate the relationship between the shape of the lateral wall and the early failure of internal fixation in the fracture of the femoral trochanteric region(FFT)., Methods: Total 295 patients with femoral trochanteric fracture underwent internal fixation from January 2015 to January 2020 were selected. The patients were divided into two groups according to whether there was early internal fixation failure after surgery, 19 patients in the failure group and 276 patients in the normal group. Gender, affected side, age, AO classification, body mass index(BMI), preoperative hemoglobin, X-ray measurement of lower lateral wall thickness, preoperative internal diseases, intraoperative blood loss, postoperative tip apex distance(TAD), postoperative neck shaft angle, operation time and other data were compared between two groups. The shape of the lateral wall was compared between two groups, and the correlation between the shape of the lateral wall and the early internal fixation failure of femoral trochanteric fracture was analyzed., Results: All patients were followed up for more than 1 year. There was no significant difference between two groups in terms of intraoperative blood loss, operation time, postoperative TAD, and postoperative neck shaft angle( P >0.05). At the latest follow-up, the visual anaglue scale (VAS) of the failure group was higher than that of the normal group( P <0.01), and the Harris score of the failure group was lower than that of normal group( P <0.05). The receiver operator characteristic (ROC) curve between shape of lateral wall and failure of early internal fixation of femoral trochanteric fracture was drawn. The critical value of the midpoint lateral wall thickness was 16.5 mm, and the area under the ROC curve was 0.845;The critical value of average sidewall thickness was 16.5 mm, and the area under ROC curve was 0.838;The critical value of the axial area of the sidewall was 7.5 mm, and the area under the ROC curve was 0.826., Conclusion: The shape of the lateral femoral wall measured by CT could be used as a predictive factor for the early failure of internal fixation of femoral trochanteric fractures. For patients at risk, more reasonable surgical plans and postoperative preventive measures should be developed.

Introduction: Exposure to road traffic noise has been reported to be associated with depression in many epidemiological studies, but the association between noise frequency spectrum and depression remains unclear. This community-based study investigated the associations between road traffic noise exposure and its frequency components with prevalent depression., Methods: A total of 3,191 residents living in Taichung who participated in the Taiwan Biobank between 2010 and 2017, were included as study participants. The land-use regression models were used to evaluate individual annual average values of A-weighted equivalent sound level over 24 h (L eq,24h ) and particulate matter with an aerodynamic diameter <2.5 μm (PM 2.5 ) using the geographic information system. Multiple logistic regression was applied to estimate the odds ratios (ORs) for depression after adjusting for potential risk factors and PM 2.5 ., Results: An interquartile range increase in L eq,24h at full frequency (4.7 dBA), 1,000 Hz (5.2 dB), and 2,000 Hz (4.8 dB) was significantly associated with an elevated risk for depression with ORs of 1.62 (95% confidence interval [CI]: 1.03, 2.55), 1.58 (95% CI: 1.05, 2.37), and 1.58 (95% CI:1.03, 2.43), respectively, by controlling for PM 2.5 . The high-exposure group (≥3rd quartile median of noise levels) at full frequency, 1,000 Hz, and 2,000 Hz had an increased risk for depression with ORs of 2.65 (95% CI: 1.16-6.05), 2.47 (95% CI: 1.07-5.70), and 2.60 (95% CI: 1.10-6.12), respectively, compared with the reference group (<1st quartile of noise levels) after adjustment for PM 2.5 . Significant exposure-response trends were observed between the prevalent depression and noise exposure by quartiles at full frequency, 1,000 Hz, and 2,000 Hz (all p < 0.05)., Conclusion: Exposure to road traffic noise may be associated with an increased prevalence of depression, particularly at 1,000 and 2,000 Hz., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Cheng, Wu and Chang.)

Depression is a serious mental illness, mainly characterized as large mood swings and sleep, diet, and cognitive function disorders. NLPR3, one of the inflammasomes that can be activated by a variety of stimuli to promote the maturation and secretion of pro-inflammatory cytokines, has been considered to be involved in the pathophysiology of depression. In this study, the putative role of CY-09, a selective and direct inhibitor of NLRP3, was evaluated in the lipopolysaccharide (LPS)-induced mice. The results of the study indicated that CY-09 significantly decreased the levels of NLRP3 in the hippocampus of LPS-induced mice. In addition, CY-09 increased the sucrose preference and shortened the immobility time in LPS-induced mice, suggesting the antidepressant-like effects of inhibiting NLRP3 inflammasome. Biochemical analysis showed that LPS significantly activated the NLRP3/ASC/cytokine signaling pathway and caused microglial activation, while CY-09 prevented the changes. Moreover, CY-09 increased the brain-derived neurotrophic factor (BDNF) only in microglia but not in the whole hippocampus. Meanwhile, CY-09 did not promote neurogenesis in the hippocampus of LPS mice. In conclusion, the results of the study showed that the antidepressant-like effects of NLRP3 inhibitor CY-09 were mediated by alleviating neuroinflammation in microglia and independent of the neurotrophic function in the hippocampus.

Background: No reports on Letrozole as a pretreatment before ablation of uterine fibroid with high intensity focused ultrasound (HIFU), so a retrospective observation study was performed to evaluate the response of different pre-HIFU medication., Methods: We collected patients with single uterine fibroid receiving HIFU ablation from January 2018 to April 2021. All enrolled patients were classified into three group: group A (no pre-HIFU medication use), group B (Pre-HIFU letrozole use), group C (pre-HIFU gonadotrophin releasing hormone analog, GnRHa). Further associated clinical data and treatment response after HIFU treatment were reviewed and evaluated., Results: A total of 39 patients including 21, 7, and 11 in group A, B, and C were collected respectively. After pre-HIFU medication, no difference of fibroid volume was found (A: 251.4, B: 360.6, C: 409.4 cm 3 , p = 0.250), and GnRHa group had significantly larger volume reduction than Letrozole users (38.6% vs. 16.4%, p = 0.007). The incidence of hypoestrogenic symptoms was higher in GnRHa group than in letrozole users (27.3% vs. 0, p = 0.170). GnRHa group had more sonication time ( p = 0.001), treatment duration ( p = 0.002), and ablated energy ( p = 0.001) than group A and B. The treatment efficiency was higher in letrozole group than that in other 2 groups (4.52 vs. 2.39 vs. 2.34 cm 3 /min, p = 0.050). For patients with fibroid over 10 cm in diameter, letrozole group had even better energy efficiency ( p = 0.067), treatment speed ( p = 0.007), treatment efficiency ( p = 0.001), NPV per energy ( p = 0.005), and NPV per sonication ( p = 0.004) than other 2 groups., Conclusion: Letrozole as a pretreatment medication before HIFU treatment might increase the energy efficiency and treatment efficiency of its ablation of uterine leiomyoma, especially for fibroid over 10 cm. Future study of larger patient number is needed to confirm our results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Hsu, Huang, Cheng, Chang and Chou.)

Objective: To investigate the relationship between the area of psoas major muscle(PMI) and recurrent contralateral hip fracture in the initial intertrochanteric fracture., Methods: Total of 87 patients with intertrochanteric fracture of femur from January 2008 to January 2011 were selected for CT scanning of lumbar spine and hip at the time of the first fracture, and then divided into two groups according to whether there was fracture in the contralateral hip, 13 patients in the contralateral hip fracture group, 5 males and 8 females, aged(82.30±5.66) years;there were 74 cases in the non contralateral hip fracture group, including 32 males and 42 females, with an age of (79.70±5.84) years. The gender, age, preoperative blood albumin value, operation side, body mass index(BMI), Harris score of hip joint one year after operation, Barthel index before operation and medical diseases before operation were observed and compared between two groups. The PMI was used to compare the area of psosa major on CT before operation in two groups, and the correlation between the area of PMI at the time of initial fracture and the fracture of the contralateral hip was evaluated., Results: The two groups were followed up for more than 2 years after operation. There was a significant difference in PMI between two groups( P <0.05). There was a significant positive correlation between preoperative PMI and the time of re fracture of the contralateral hip( r =0.641, P =0.018)., Conclusion: There are differences in the area of PMI in patients with contralateral hip fracture, so the area of PMI can be regarded as an important risk factor for contralateral hip fracture.

This cross-sectional study aimed to explore the influence of the COVID-19 pandemic on physical activity (PA) and dietary habits, and their impact on body weight changes during the Level 3 alert period that resulted in the lockdown in Taiwan. The study was conducted between 1 July 2021 and 15 July 2021, using a Google Forms online survey platform. Personal data, anthropometric information, PA information, and dietary habit information were collected before and during the alert period. Exactly 374 respondents, aged between 20 and 66, were included in the study. The results indicate that the lockdown during the alert period negatively impacted all levels of PA, including vigorous and moderate activities and walking. Additionally, respondents showed a sedentary lifestyle, with an increased daily sitting time of 22%. However, body weight and dietary behavior were not significantly affected, and some dietary questions achieved significant differences, including eating three meals less regularly, among others. During the pandemic, exercise was still one of the most important ways to maintain health; therefore, we hope to bring more attention to the prevention of sedentary lifestyles and dietary abnormalities in Taiwan during a pandemic.

With the development of high-density and high-rise buildings on both sides of the street, widespread attention has been paid to the applicability of the traditional greening model of 'the more trees, the better atmospheric environment' in dealing with air pollution in urban street canyons. Clarifying the characteristics of street canyons greening and its planting design pattern on the reduction of emission pollutants by vehicles is an important prerequisite for the improvement of air quality in the street canyons. Based on literature review, we compared the applicability and limitations of the three methods, including field observation, wind tunnel test, and numerical simulation. We further analyzed the effects of roadside trees and hedges on the dispersion and deposition of air pollutants, and put forward a framework of adaptive greening design for air quality improvement. Finally, we proposed that future studies should address the creation of graphic languages for roadside greening design, the development of technical guidelines for evaluating the exposure of air pollution, and the optimization of parameterization schemes for the physical processes of greening effect in computational fluid dynamics models. Overall, our review could provide ideas and reference for the subsequent research.

Workplace violence is recognized as a serious psychosocial work hazard in the workplace. Nurses face higher risks of workplace violence and poor mental health than other medical professionals. In addition to addressing personal factors, workplace violence should be understood and managed in the context of the organizational climate. In this article, the definition and types of workplace violence and a socio-ecological perspective on workplace violence are introduced. In addition, the prevalence and impact on mental health of workplace violence are described. Lastly, the concept of safety climate and its influence on mental health are proposed. We hope this article provides readers with a better understanding of workplace violence and a contextual perspective on this issue. In addition to understanding workplace violence and learning coping strategies and skills, hospital managers should promote a positive climate of safety to reduce the occurrence of workplace violence and the impact of workplace violence on nurses.

Social jetlag, the discrepancy between social and biological timing, has been suggested to disturb metabolic functions. However, the relationship between social jetlag and obesity has been inconsistent in other studies. In this study we examined the association between social jetlag and obesity among day and shift workers. We invited 2508 day workers and 1383 shift workers from a hospital worker health cohort to participate in a 2018-2019 survey on their sleep behaviors. Shift-specific social jetlag was quantified using the Munich ChronoType Questionnaire, and body mass index was measured during annual physical examinations. The distributions of shift-specific social jetlag were illustrated, and logistic regression analysis was used to examine the association between social jetlag and obesity. We found that high level of social jetlag (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.08-1.47) and positive social jetlag (OR = 2.25, 95% CI = 1.30-3.90) during evening shifts were associated with obesity after adjustment for age, sex, health behaviors, and sleep quality. During night shift periods, sleep time varied greatly on free days, but the participants slept at similar times, namely 16:00, on workdays. In conclusion, phase advance on workdays and high levels of social jetlag were associated with obesity. Sleep timing should therefore be recommended according to the relative phase of individuals' preferred sleep time and work time.

Objective: To analyze and compare the clinical efficacy of F-shaped hollow screw and traditional inverted triangle three parallel screws in the treatment of young and middle-aged Pauwels type Ⅲ femoral neck fracture., Methods: From January 2017 to January 2020, 38 patients with Pauwels type Ⅲ femoral neck fracture were treated. They were divided into two groups according to different screw placement methods. Among them, 18 patients in group A were fixed with F-shaped hollow screw, including 12 males and 6 females, aged 37 to 55 years, the time from injury to operation was 1 to 3 days. Other 20 cases in group B were fixed with 3 parallel screws in traditional inverted triangle, including 12 males and 8 females, aged 35 to 55 years. The time from injury to operation was 1 to 3 days. The fracture nonunion, femoral head necrosis, femoral neck shortening, hollow screw withdrawal, hip function Harris score and visual analogue scale(VAS) of pain were compared between the two groups., Results: All patients were followed up for 15 to 31 months. There was no significant difference in fracture nonunion, femoral neck shortening and femoral head necrosis between two groups( P >0.05). There was significant difference in screw withdrawal between two groups( P <0.05). There was no significant difference in hip Harris score and VAS between the two groups at 12 months after operation( P >0.05)., Conclusion: The short-term and medium-term effects of F-shaped and traditional inverted triangle three parallel screws in the treatment of young and middle-aged Pauwels Ⅲ femoral neck fractures are similar, but the nail withdrawal rate of F-shaped hollow screw is low.

Aging is a major challenge facing modern society and has attracted global attention. Studies have provided some initial evidence that health literacy plays a role in determining frailty; however, most of these studies have used small convenience samples of individuals recruited from geographically limited areas, thus limiting the generalizability of their findings. The present study explored the relationships among health literacy, exercise, and frailty in Taiwanese older adults by using the data of a national population-based survey. We retrieved data from the Taiwan Longitudinal Study on Aging, a population-based survey. We gathered the 2015 data on the age, sex, education level, marital status, exercise habits, and activities of daily living (ADLs) of each eligible respondent. We evaluated the respondents' health literacy by using a nine-item health literacy scale and categorized their health literacy level as low, medium, or high. Frailty was diagnosed according the Fried criteria. Our final sample consisted of 7702 community-dwelling older adults (3630 men and 4072 adults). Of these, 25.3% had low health literacy. The proportion of respondents who had two or more disabilities in terms of ADLs or instrumental ADLs was higher among the women (36.4% and 12.6%, respectively), and regular exercise was more common among the men (19.6%). Frailty was more prevalent among the women; the prevalence of frailty among the male and female respondents was 4.5% and 8.1%, respectively. High health literacy and regular exercise were protective factors for frailty. According to our results, poor health literacy is a risk factor for prefrailty and frailty, and regular exercise is significantly negatively associated with prefrailty and frailty. Additional studies are necessary to define practical strategies for reducing the risks of disability and death for older adults with low health literacy who do not exercise regularly, thereby improving their quality of life.

Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.